Coronaviruses can cause disease in animals such as humans. SARS (Severe Acute Respiratory Syndrome) is one example of such a disease. Recently, a new coronavirus has emerged, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which is associated with human fatalities. MERS-CoV has been identified as a “threat to global health” by the World Health Organization (WHO), and has been reported in 21 countries in the Middle East and Europe. MERS-CoV is a highly pathogenic respiratory virus that causes severe respiratory distress and potentially renal failure in infected individuals [1, 2].
Coronaviruses attach to the membrane of cells via interaction of their Spike (S) glycoproteins on the surface of the virion with their cognate receptor on host cells (e.g. dipeptidyl peptidase 4 (DPP4), found on a variety of human cells including lung and kidney cells). The S glycoprotein consists of an N-terminal 51 domain that contains the receptor binding domain (RBD) and an S2 domain responsible for virus-cell fusion. The MERS-CoV RBD consists of a core domain that has been co-crystallized with the human DPP4 protein, showing that it interacts with blades 4 and 5 of DPP4 [11]. In other coronaviruses, including SARS-CoV, antibodies to the RBD are able to neutralize and inhibit growth of the virus in vitro [12-14]. In mouse models of SARS-CoV, vaccine induced and passively transferred neutralizing antibodies have proven to be effective in inhibiting lung pathogenesis and death [15]. However, Antibody Dependent Enhancement (ADE) in human immune cells has been reported for SARS CoV in vitro though its clinical significance in vivo is unknown.
Human convalescent plasma and/or immunoglobulin has been used effectively to prevent and treat many viral infectious agents [16]. Public Health England and the International Severe Acute Respiratory & Emerging Infection Consortium (ISARIC) identified passive immunotherapy with neutralizing antibodies (including convalescent plasma) as a MERS-CoV treatment approach that warrants priority study. However, production of large quantities of anti-pathogen human plasma and/or immunoglobulin with high affinity and avidity antibodies currently requires donations by convalescent humans that can limit widespread availability of these human derived products for a number of cultural, infrastructure, and logistical reasons. Alternative means to rapidly produce specific human polyclonal immunoglobulin to prevent and treat infectious agents, including MERS-CoV, are needed.